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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Statin reduces cerebrovascular events independent of its cholesterol lowering effect. We hypothesized that statin inhibits early atherosclerotic change in common carotid artery (CCA), and investigated its effect on lectin-like oxidized-LDL receptor-1 (LOX-1) and monocyte chemoattractant protein-1 (MCP-1) expression, both of which are early atherosclerotic markers. Stroke-prone spontaneous hypertensive rats (SHR-SP) of 8 weeks old were orally treated with vehicle or simvastatin (20mg/kg) daily. After 4 weeks of simvastatin or vehicle treatment, or 2 weeks of vehicle and 2 weeks of simvastatin treatment, CCA was removed. LOX-1 and MCP-1 expression as well as macrophage infiltration were histologically investigated. Lipid deposition was also investigated by Sudan III staining. Simvastatin groups showed significantly smaller amount of lipid deposition and LOX-1 and MCP-1 expression, independent of serum lipid levels. Macrophage infiltration was also decreased. Reduction of cerebrovascular events by statins may be brought by the direct inhibition of atherosclerotic change.
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PMID:Macrophage infiltration, lectin-like oxidized-LDL receptor-1, and monocyte chemoattractant protein-1 are reduced by chronic HMG-CoA reductase inhibition. 1804 52

Statins belong to a class of drugs known to inhibit 3-hydroxy 3-methylglutaryl coenzyme A reductase, and block hepatic cholesterol synthesis. Since the initial statin was approved by the Food and Drug Administration in 1987, these agents quickly became the gold standard for treatment of hypercholesterolemia. Effective lipid-lowering has been found to improve the long-term prognosis of patients with coronary artery disease. In addition, statins have also been found to be highly effective in primary and secondary stroke prevention among medically managed patients with cardiovascular disease, and it appears that this benefit is largely due to the non-cholesterol-lowering, so-called pleiotropic, effects of statins. During the past decade, agents such as beta-blockers, aspirin, or other antiplatelet medications have proven to reduce the incidence of adverse postoperative outcomes among vascular surgical patients, and have rightfully assumed a place in our overall therapeutic armamentarium. There is growing evidence that statins may be especially effective in reducing cardiovascular morbidity and improving outcomes after major vascular surgery. A recent study from Johns Hopkins Hospital demonstrated a threefold reduction in the rate of perioperative stroke (P < .05) and fivefold reduction of perioperative mortality (P < .05) among 1,566 patients undergoing carotid endarterectomy (CEA). This benefit was confirmed in a series of 3,360 CEAs performed at multiple hospitals throughout Western Canada. Statin use was independently associated with a 75% reduction (odds ratio [OR] = 0.25; 95% confidence interval [CI], 0.07-0.90) in the odds of death and 45% reduction (OR = 0.55; 95% CI, 0.32-0.95) in the odds of ischemic stroke or death among patients with symptomatic carotid disease. Further, there is some data indicating that statin use may reduce long-term incidence of restenosis following CEA. Preliminary work indicates that a similar benefit of statin use in reducing neurologic morbidity among patients undergoing carotid angioplasty and stent procedures. A number of the pleiotropic effects of statin medications may be responsible for these clinical observations. Further work is necessary to better elucidate these mechanisms, as well as to determine the optimal agents, dosing, and timing of drug administration among patients undergoing carotid interventions.
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PMID:The effect of statin medications on perioperative and long-term outcomes following carotid endarterectomy or stenting. 1808 42

Atherothrombosis of the coronary and cerebral vessels is understood to be a disorder of inflammation and innate immunity, as well as a disorder of lipid accumulation. From a vascular biology perspective, the processes of cellular adhesion, monocyte and macrophage attachment, and transmigration of immune cells across the endothelium are crucial steps in early atherogenesis and in the later stages of mature plaque rupture, particularly the transition of unstable plaque at the time of acute thrombosis. There is abundant clinical evidence demonstrating that many biomarkers of inflammation are elevated years in advance of first ever myocardial infarction (MI) or thrombotic stroke and that these same biomarkers are highly predictive of recurrent MI, recurrent stroke, diabetes, and cardiovascular death. In daily practice, the inflammatory biomarker in widest use is high-sensitivity C-reactive protein (hsCRP); when interpreted within the context of usual risk factors, levels of hsCRP <1, 1 to 3, and >3 mg/l denote lower, average, and higher relative risk for future vascular events. Risk-prediction models that incorporate hsCRP, such as the Reynolds Risk Score, have been developed that improve risk classification and the accuracy for global risk prediction, particularly for those deemed at "intermediate risk" by usual algorithms, such as the Framingham Risk Score. With regard to cerebral vessels, increased biomarkers of inflammation, including hsCRP, have been associated with increased stroke risk as well as an increased rate of atherosclerosis progression in the carotid vessels. Although the proportion of variation in hsCRP explained by genetic factors may be as large as 20% to 40%, diet, exercise, and smoking cessation remain critical tools for risk reduction and CRP reduction. Statin therapy reduces hsCRP in a largely low-density lipoprotein (LDL)-independent manner, and the "anti-inflammatory" properties of these agents have been suggested as a potential mechanism beyond LDL reduction for the efficacy of these agents. The ongoing multinational Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial of 17,802 initially healthy men and women with low levels of LDL cholesterol but increased levels of hsCRP will help to define whether vascular protection can be achieved with statin therapy, even in the absence of hyperlipidemia. Targeted anti-inflammatory therapies are being developed that may provide a direct method of translating the biology of inflammation into new clinical treatments across multiple vascular beds. This article summarizes data supporting a role for inflammation in cardiovascular disease and offers the possibility that other disorders characterized by inflammation, such as periodontal disease, may have an indirect role by influencing the risk, manifestation, and progression of vascular events.
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PMID:Inflammation, C-reactive protein, and atherothrombosis. 1867 9

Statin's treatment clearly is authorized in prevention of coronary heart disease (CHD). According to the results of many studies and meta-analyses statins can inhibit the first cerebrovascular infarct (stroke). The greater the decrease of LDL-cholesterol level the more prominent the efficacy. The effect is not so robust compared to coronary vessels moreover clear pleiotropic (cholesterol independent) action takes also part. It has been nowadays revealed that high dose (80 mg) atorvastatin can confine first time the development of recurrence stroke (SPARCL study), which is an important fact in the field of secondary prevention.
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PMID:[Important aim of statin therapy: ischemic cardiovascular event (stroke)]. 1876 79

Statin therapy in patients with coronary artery disease or in those at risk for cardiovascular disease is associated with a reduced incidence of ischemic stroke. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial showed treatment with atorvastatin 80 mg daily in patients with a recent stroke or transient ischemic attack (TIA) reduces the incidence of fatal and nonfatal stroke by 16%. In this population with a recent stroke or TIA, coronary artery disease events and the need for revascularization were a frequent occurrence. Furthermore, the relative reduction of noncerebrovascular events and the need for revascularization was greater with atorvastatin than the reduction of stroke. A patient with a recent ischemic stroke or TIA is at high risk for fatal and nonfatal coronary events (approximately 4% per year), and according to most guidelines for the management of coronary artery disease, such patients should be in the high risk category. Consequently, ischemic stroke should be considered to be a coronary risk equivalent with a prognosis similar to that of a patient with coronary artery disease. Furthermore, both the stroke and coronary artery disease prognoses are improved by treatment with atorvastatin 80 mg daily.
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PMID:Ischemic stroke: a cardiovascular risk equivalent? Lessons learned from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. 1878 21

Secondary prevention of cardiovascular disease after carotid endarterectomy should include management of low-density lipoprotein (LDL) levels, but increased LDL levels are undertreated in these patients. We examined trends in statin use and LDL goal achievement in veterans undergoing carotid endarterectomy (CEA), a medically high-risk group with high rates of cardiovascular morbidity and mortality. The records of all CEA performed between 1995 and 2005 in the Connecticut Veterans' Affairs (VA) hospital were reviewed. Kaplan-Meier analysis was used to analyze long-term outcomes. ANOVA was used for comparisons between groups. A total of 309 CEA procedures were performed in 298 patients. The mean follow-up was 4.1 years. Statin use increased over time (12% in 1995, 84% in 2005) and mean LDL levels decreased (105 mg/dl in 1997, 90 mg/dl in 2007). The number of patients achieving LDL goals of 100 mg/dl or 70 mg/dl increased. Mean HDL levels decreased (53 mg/dl in 1997 and 38 mg/dl in 2007). Patients with three or more comorbid medical conditions were more likely to achieve LDL goals. At 12 years, freedom from stroke was 91%, freedom from myocardial infarction was 46% and survival was 12%. In conclusion, over the last decade, among patients who have undergone CEA, statin use has increased and LDL levels have improved.
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PMID:Lipid goal achievement and trends in lipid-lowering therapy in veterans undergoing carotid endarterectomy. 1914 76

Post-stroke levels of total cholesterol (TC) appear to be negatively associated with stroke mortality. Statin pretreatment might affect this association. Sex differences in the prognostic value of the lipid profile have not yet been studied. We have evaluated the impact of TC, high- and low-density lipoprotein (HDL and LDL, respectively), and triglyceride (TG) levels on the 3-month outcome after a first ischemic stroke (IS) according to sex and previous statin use. The study group consisted of a hospital-based cohort of consecutive patients with a diagnosis of first IS. Poor outcome was defined as a modified Rankin Scale (mRS) score >or=3 at 90 days. The odds ration (OR) for poor prognosis was analyzed for each sex using logistic regression models adjusted for vascular risk factors and statin pretreatment. A total of 591 patients were included in the analysis (318 men). The predictors of a 90-day poor outcome were age and initial NIH Stroke Scale (NIHSS) score in women, and age, initial NIHSS, smoking, atrial fibrillation, and thrombolytic treatment in men. In women, none of the lipids studied affected the 90-day prognosis. Men falling in the last quintile of TC [OR: 0.68 95% confidence interval (95% CI) 0.52-0.88; p = 0.004] and LDL (OR 0.74, 95% CI 0.56-0.98; p = 0.04) have better outcome than men in the first quintile. Adjusting for statin pretreatment did not change the results. The results indicated that an association between poststroke lipids and prognosis may vary by sex. In women, lipids were not associated with the outcome; in men, lower TC and LDL were associated with worse prognosis. These differences can not be explained by statin use and require further research.
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PMID:Sex differences in the prognostic value of the lipid profile after the first ischemic stroke. 1925 78

Despite the inconsistent or weak association between cholesterol and stroke, lowering of cholesterol concentrations with statins reduces the risk of stroke in high-risk populations and in patients with non-cardioembolic stroke or transient ischaemic attack. Statin therapy is the most important advance in stroke prevention since the introduction of aspirin and antihypertensive treatments. Meta-analysis of randomised trials of statins in combination with other preventive strategies, including 165 792 individuals, shows that each 1 mmol/L (39 mg/dL) decrease in LDL cholesterol equates to a reduction in relative risk for stroke of 21.1% (95% CI 6.3-33.5, p=0.009). In secondary prevention of non-cardioembolic stroke, intense reduction of LDL cholesterol by statins also significantly reduced the risk of recurrent stroke (relative risk 0.84, 0.71-0.99, p=0.03) and major cardiovascular events (0.80, 0.69-0.92, p=0.002). Future directions include assessment of a target LDL cholesterol concentration of less than 1.8 mmol/L (70 mg/dL), the effects of triglyceride-lowering therapy alone or in combination with statins, and the effects of treatments to raise HDL cholesterol concentrations.
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PMID:Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention. 1937 63

Since pravastatin, a HMG-CoA reductase inhibitor, has recently been shown to reduce infarct volumes and glutamate release in a rat model of ischemic stroke, the aim of the present study was to investigate whether this neuroprotective effect may be due to a modulation of excitatory and inhibitory neurotransmitter receptors. Therefore, Wistar rats were treated six times in 4 days with pravastatin or saline and allowed to survive for 6 hours or 5 days (n=10 per time point and group), respectively. Using quantitative receptor autoradiography, ligand binding densities of [(3)H]MK-801, [(3)H]AMPA, and [(3)H]muscimol for labeling of NMDA, AMPA, and GABA(A) receptors were analyzed in sensorimotor cortices Par1 and Par2, the striatum, and the hippocampus. Statin therapy induced complex alterations of ligand binding densities in different brain regions. Labeling of NMDA receptors was significantly increased in Par2, both after 6 hours and 5 days, respectively. Within the striatum, AMPA as well as GABA(A) receptor binding values were significantly increased on day 5. Furthermore, a marked and significant increase of [(3)H]muscimol ligand binding to GABA(A) receptors throughout all hippocampal subfields was seen after 6 hours. This complexity could easily be unraveled when focusing on the balance between excitatory glutamate and inhibitory GABA(A) receptors, in which case only the increase of hippocampal [(3)H]muscimol ligand binding 6 hours after the first application of pravastatin was accompanied by a net shift towards inhibition. Consequently, our data suggest an additional regulatory pathway induced by statins, namely modification of the abundance of excitatory and inhibitory neurotransmitter receptors.
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PMID:Pravastatin treatment causes a shift in the balance of hippocampal neurotransmitter binding densities towards inhibition. 2002 13

Statin therapy in patients with cardiovascular disease is associated with reduced incidence of stroke. The Stroke Prevention by Aggressive Reduction of Cholesterol Levels (SPARCL) trial showed daily treatment with 80 mg of atorvastatin in patients with a recent stroke or transient ischemic attack (TIA) reduced the incidence of fatal or nonfatal stroke by 16%. Several post hoc analyses of different subgroups followed the SPARCL study. They have not revealed any significant differences when patients were sorted by age, sex, presence of carotid disease or type of stroke, with the exception of intracranial hemorrhage as the entry event. Lower low-density lipoprotein cholesterol levels in addition to possible neuroprotective mechanisms due to atorvastatin treatment correlate with improved risk reduction. Although not predefined subgroups and subject to an insufficient power, these post hoc studies have generated new clinical questions. However, clinicians should avoid denying therapy based on such subgroup analysis. At this point, the best evidence powerfully demonstrates stroke and TIA patients should be prescribed high dose statin therapy for secondary stroke prevention.
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PMID:Atorvastatin in stroke: a review of SPARCL and subgroup analysis. 2040 30


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